Targeting the cyclin dependent kinase and retinoblastoma axis overcomes standard of care resistance in BRAF ^V600E -mutant melanoma.

ABSTRACT: Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAF^V600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression. The rationale for this is that the retinoblastoma protein (pRb) is 95% wildtype in BRAF mutant melanoma. We discovered that 77/77 stage IV metastatic melanoma tissues were pos

SUBMITTER: Harris AL 

PROVIDER: S-EPMC5834273 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature